{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T19:40:22Z","timestamp":1786390822594,"version":"build-2736575974"},"reference-count":63,"publisher":"Wiley","issue":"18","license":[{"start":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T00:00:00Z","timestamp":1783296000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T00:00:00Z","timestamp":1783296000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2024A1212110282"],"award-info":[{"award-number":["2024A1212110282"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82272236"],"award-info":[{"award-number":["82272236"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82404643"],"award-info":[{"award-number":["82404643"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82502611"],"award-info":[{"award-number":["82502611"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2022A1515012567"],"award-info":[{"award-number":["2022A1515012567"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>Sepsis, a life\u2010threatening organ dysfunction caused by a dysregulated host response to infection, frequently leads to long\u2010term cognitive impairment. Tangeretin, a polymethoxylated citrus flavonoid, has neuroactive and anti\u2010inflammatory properties. We investigated whether tangeretin protects against sepsis\u2010associated neurocognitive deficits and delineated the underlying mechanisms, focusing on Akt signalling and microglial metabolism.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>\n                      Sepsis was induced by caecal ligation and puncture in mice. Tangeretin (15 or 30\u2009mg\u00b7kg\n                      <jats:sup>\u22121<\/jats:sup>\n                      \u00b7day\n                      <jats:sup>\u22121<\/jats:sup>\n                      , intraperitoneal) was initiated immediately after surgery and maintained throughout the study. Cognitive function was assessed by Morris water maze and novel object recognition. Hippocampal microglial activation and neuroinflammation were quantified. In vitro, BV2 cells and primary microglia were exposed to lipopolysaccharide (\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/www.guidetopharmacology.org\/GRAC\/LigandDisplayForward?ligandId=5019\">LPS<\/jats:ext-link>\n                      , 1\u00a0\u03bcg\u00b7ml\n                      <jats:sup>\u22121<\/jats:sup>\n                      ) with\/without tangeretin (40\u2009\u03bcM) to measure cytokine production, migration and Akt activity. Direct tangeretin\u2010Akt interaction was tested by surface plasmon resonance and cellular thermal shift assay. Metabolic readouts focused on glycolysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>Tangeretin improved sepsis\u2010induced cognitive deficits, decreased hippocampal microglial activation, and lowered proinflammatory cytokine levels and microglial migration. It exerted anti\u2010inflammatory effects via inhibition of the Akt pathway, and pharmacological Akt activation blocked these effects. Surface plasmon resonance and cellular thermal shift assay showed hat tangeretin binds Akt. Metabolically, tangeretin reduced LPS\u2010induced glycolysis (decreased extracellular acidification rate and glycolytic capacity), consistent with diminished Akt phosphorylation and microglial activation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and Implications<\/jats:title>\n                    <jats:p>Tangeretin mitigates sepsis\u2010associated neuroinflammation and cognitive impairment by targeting microglial Akt signalling and restraining glycolytic reprogramming. These data support tangeretin as a mechanistically informed candidate for adjunctive therapy in sepsis\u2010related neurocognitive dysfunction.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70477","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T07:43:07Z","timestamp":1783323787000},"page":"5676-5697","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Tangeretin ameliorates sepsis\u2010induced neurocognitive impairment in adult male mice by suppressing Akt\u2010driven glycolytic reprogramming and neuroinflammation"],"prefix":"10.1111","volume":"183","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9818-1089","authenticated-orcid":false,"given":"Juexian","family":"Wei","sequence":"first","affiliation":[{"name":"Department of Emergency Guangzhou Institute of Emergency Medicine, the Second Affiliated Hospital, Guangzhou Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haifeng","family":"Mao","sequence":"additional","affiliation":[{"name":"Department of Emergency Guangzhou Institute of Emergency Medicine, the Second Affiliated Hospital, Guangzhou Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hengzong","family":"Mo","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine The Second Clinical School, Guangzhou Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Emergency Guangzhou Institute of Emergency Medicine, the Second Affiliated Hospital, Guangzhou Medical University  Guangzhou China"},{"name":"School of Pharmaceutical Sciences Guangzhou Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ehua","family":"Deng","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Guangzhou Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aijia","family":"Zhong","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Guangzhou Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyan","family":"Tang","sequence":"additional","affiliation":[{"name":"Meizhou Academy of Medical Science, Meizhou People's Hospital (Huangtang Hospital)  Meizhou China"},{"name":"Affiliated Meizhou Hospital of Shantou University Medical College  Meizhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Senwen","family":"Liu","sequence":"additional","affiliation":[{"name":"The Third Affiliated Hospital of Sun Yat\u2010Sen University\u00b7Yuedong Hospital  Meizhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiqing","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Emergency Guangzhou Institute of Emergency Medicine, the Second Affiliated Hospital, Guangzhou Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haojun","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Emergency Guangzhou Institute of Emergency Medicine, the Second Affiliated Hospital, Guangzhou Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huilin","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Emergency Guangzhou Institute of Emergency Medicine, the Second Affiliated Hospital, Guangzhou Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shao\u2010Peng","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Emergency Guangzhou Institute of Emergency Medicine, the Second Affiliated Hospital, Guangzhou Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohui","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Emergency Guangzhou Institute of Emergency Medicine, the Second Affiliated Hospital, Guangzhou Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,6]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.70234"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.70229"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.envint.2019.105428"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1039\/d5ra03091a"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(14)70246-2"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.112.000024"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awab475"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.2174\/1871527316666170328113309"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2008.112797"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.17441"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.3791\/62237"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-018-1250-1"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2019.04.047"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1177\/0885066617719750"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.28721"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2249"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-015-0332-6"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M506850200"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2014.138"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2015.00051"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1039\/d1fo02989d"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.12979"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2017.69"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-022-01131-7"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2022.10.299"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.600421"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.21769\/BioProtoc.1989"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15178"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41401-021-00634-3"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/sigtrans.2017.23"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.08.040"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201712-2593ED"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2020.10.008"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph14050416"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-13581-z"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2006.01.010"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18030489"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13139"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3000410"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/dneu.22253"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10787-023-01167-3"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2016.0289"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2020.09.018"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1186\/1756-0500-7-233"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fitote.2011.08.010"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.01206.2005"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-017-4807-z"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2013.177"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biosystems.2014.11.005"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1080\/14787210.2020.1812384"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2013.01.067"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41401-020-00583-3"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12979-019-0158-7"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(14)70017-1"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1139\/cjpp-2017-0243"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-025-06635-8"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.929316"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10753-020-01303-z"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.3791\/57648"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-42286-8"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-017-0648-1"},{"key":"e_1_2_11_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2016.06.036"},{"key":"e_1_2_11_64_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-019-1651-9"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.70477","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/bph.70477","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.70477","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T19:12:27Z","timestamp":1786389147000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bph.70477"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,6]]},"references-count":63,"journal-issue":{"issue":"18","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1111\/bph.70477"],"URL":"https:\/\/doi.org\/10.1111\/bph.70477","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,6]]},"assertion":[{"value":"2025-08-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}